April 6, 2011 (Colorado Springs, Colorado) — Clozapine may reduce cannabis use among patients with schizophrenia and co-occurring cannabis use disorder, according to results of a randomized controlled study presented this week at the 13th International Congress on Schizophrenia Research in Colorado Springs, Colorado.
Cannabis use disorders, seen in up to 40% of people with schizophrenia, can exacerbate clinical symptoms and lead to noncompliance with medication, relapse, and hospitalization. Preliminary uncontrolled studies provide some evidence that patients taking clozapine, but not other atypical antipsychotics, have higher rates of remission from cannabis and alcohol use disorders.
"We do think there is something different with clozapine," study investigator Mary Brunette, MD, associate professor of psychiatry, Dartmouth Medical School, Hanover, New Hampshire, told Medscape Medical News.
"For example, our group at Dartmouth showed in about 230 people that we followed prospectively for 10 years, those that were put on clozapine for other reasons reduced their substance use," she said. But, until now, "no one has looked at this in a randomized controlled study."
Dr. Brunette and colleagues enrolled 31 mostly male patients with schizophrenia or schizoaffective disorder and co-occurring cannabis use disorder. The subjects' mean age was 36 years. They randomly assigned 15 subjects to switch to clozapine, whereas the other 16 continued to take their current antipsychotic medication. Investigators followed up study subjects weekly for 3 months. Medications known to limit cannabis use, such as naltrexone, were not allowed.
Fewer Joints Per Week
The researchers found that subjects taking clozapine used less cannabis than patients in the "other" antipsychotic group (P = .03).
At baseline, participants reported using cannabis a mean of 4.5 days per week and smoked a mean of 12.3 joints per week. During the study, those taking clozapine smoked about 4.5 fewer joints per week than the other patients (t = 1.77; df = 28.5; P = .086; effect size, ~0.6).
"The size of the effect is quite substantial," Dr. Brunette said, and the effect on cannabis use appears to be independent of any effect on symptoms because the 2 groups did not differ in terms of symptoms or functioning.
Animal studies suggest that clozapine's apparent "unusual" clinical effects on substance use in patients with schizophrenia may stem from its varied pharmacologic actions on dopaminergic and noradrenergic systems, the researchers note.
They propose that clozapine's weak dopamine receptor blockade, coupled with its activation of the norepinephrine system, may lessen dysfunction in the dopamine-mediated brain reward system that may underlie cannabis use disorder in this patient population.
But Dr. Brunette emphasized that clozapine is not for every cannabis-using patient with schizophrenia.
"Clozapine has a lot of side effects, some potentially dangerous. In about half a percent of people, it can suppress the bone marrow's ability to make white blood cells, so regular blood tests, at least in the beginning of treatment, are needed," Dr. Brunette said.
She added that patients taking clozapine also have to submit to close monitoring, and some individuals who are heavy substance users aren't willing to adhere to this requirement.
Nonetheless, clozapine is "something to consider" in the right patient, she said.
Dr. Brunette said she hopes to confirm these findings in a larger randomized controlled study. Her team has a grant proposal in to the National Institutes of Health for funding to perform a larger study.
The current study was funded by the National Institute on Drug Abuse. The study authors have disclosed no relevant financial relationships.
13th International Congress on Schizophrenia Research: Abstract 979673. Presented March 4, 2011.
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